A Pixel Design of a Branching Ultra-Highspeed Image Sensor.

A burst image sensor named Hanabi, meaning fireworks in Japanese, includes a branching CCD and multiple CMOS readout circuits. The sensor is backside-illuminated with a light/charge guide pipe to minimize the temporal resolution by suppressing the horizontal motion of signal carriers. On the front side, the pixel has a guide gate at the center, branching to six first-branching gates, each bifurcating to second-branching gates, and finally connected to 12 (=6×2) floating diffusions. The signals are either read out after an image capture operation to replay 12 to 48 consecutive images, or continuously transferred to a memory chip stacked on the front side of the sensor chip and converted to digital signals. A CCD burst image sensor enables a noiseless signal transfer from a photodiode to the in-situ storage even at very high frame rates. However, the pixel count conflicts with the frame count due to the large pixel size for the relatively large in-pixel CCD memory elements. A CMOS burst image sensor can use small trench-type capacitors for memory elements, instead of CCD channels. However, the transfer noise from a floating diffusion to the memory element increases in proportion to the square root of the frame rate. The Hanabi chip overcomes the compromise between these pros and cons.

Toward the Super Temporal Resolution Image Sensor with a Germanium Photodiode for Visible Light.

The theoretical temporal resolution limit tT of a silicon photodiode (Si PD) is 11.1 ps. We call "super temporal resolution" the temporal resolution that is shorter than that limit. To achieve this resolution, Germanium is selected as a candidate material for the photodiode (Ge PD) for visible light since the absorption coefficient of Ge for the wavelength is several tens of times higher than that of Si, allowing a very thin PD. On the other hand, the saturation drift velocity of electrons in Ge is about 2/3 of that in Si. The ratio suggests an ultra-short propagation time of electrons in the Ge PD. However, the diffusion coefficient of electrons in Ge is four times higher than that of Si. Therefore, Monte Carlo simulations were applied to analyze the temporal resolution of the Ge PD. The estimated theoretical temporal resolution limit is 0.26 ps, while the practical limit is 1.41 ps. To achieve a super temporal resolution better than 11.1 ps, the driver circuit must operate at least 100 GHz. It is thus proposed to develop, at first, a short-wavelength infrared (SWIR) ultra-high-speed image sensor with a thicker and wider Ge PD, and then gradually decrease the size along with the progress of the driver circuits.

Light-In-Flight Imaging by a Silicon Image Sensor: Toward the Theoretical Highest Frame Rate.

Light in flight was captured by a single shot of a newly developed backside-illuminated multi-collection-gate image sensor at a frame interval of 10 ns without high-speed gating devices such as a streak camera or post data processes. This paper reports the achievement and further evolution of the image sensor toward the theoretical temporal resolution limit of 11.1 ps derived by the authors. The theoretical analysis revealed the conditions to minimize the temporal resolution. Simulations show that the image sensor designed following the specified conditions and fabricated by existing technology will achieve a frame interval of 50 ps. The sensor, 200 times faster than our latest sensor will innovate advanced analytical apparatuses using time-of-flight or lifetime measurements, such as imaging TOF-MS, FLIM, pulse neutron tomography, PET, LIDAR, and more, beyond these known applications.

An Image Signal Accumulation Multi-Collection-Gate Image Sensor Operating at 25 Mfps with 32 × 32 Pixels and 1220 In-Pixel Frame Memory.

The paper presents an ultra-high-speed image sensor for motion pictures of reproducible events emitting very weak light. The sensor is backside-illuminated. Each pixel is equipped with multiple collection gates (MCG) at the center of the front side. Each collection gate is connected to an in-pixel large memory unit, which can accumulate image signals captured by repetitive imaging. The combination of the backside illumination, image signal accumulation, and slow readout from the in-pixel signal storage after an image capturing operation offers a very high sensitivity. Pipeline signal transfer from the the multiple collection gates (MCG) to the in-pixel memory units enables the sensor to achieve a large frame count and a very high frame rate at the same time. A test sensor was fabricated with a pixel count of 32 × 32 pixels. Each pixel is equipped with four collection gates, each connected to a memory unit with 305 elements; thus, with a total frame count of 1220 (305 × 4) frames. The test camera achieved 25 Mfps, while the sensor was designed to operate at 50 Mfps.

Oral toxicity evaluation of Bacillus clausii M31 isolated from the children's feces in the northern province of Vietnam.

This study investigated the acute and repeated 28-day dose toxicity profiles of Bacillus clausii M31, isolated from children's feces, in Swiss rats and New Zealand rabbits. To investigate acute toxicity, rats were given varied doses of B. clausii M31 (1 × 1011 CFU/mL, 3 × 1011 CFU/mL, and 5 × 1011 CFU/mL) orally once daily for 14 days, in accordance with OECD recommendations No. 423. To evaluate toxicity, rabbits were given either a low dosage (1 × 1011 CFU/mL) or a high dose (5 × 1011 CFU/mL) during a 28-day period using the OECD Test Guideline 407 protocol. Neither death nor significant abnormalities were observed in the rats during the experiment. The microscopic examination of key organs revealed no substantial changes in organ morphology. Furthermore, analyses of serum biochemistry and hematological parameters did not reveal any treatment-associated variations. In sum, these findings suggest that the oral intake of B. clausii M31 at concentrations up to 5 × 1011 CFU/mL for 28 days poses no discernible risks.

Assessing Path Dependency in Vietnam's Healthcare Legal Framework: Exploring Public-Private Collaboration in Ho Chi Minh City during the COVID-19 Crisis.

The COVID-19 pandemic prompted a nudge for public-private cooperation in healthcare to rapidly cope with limited resource. However, Vietnam's historical reliance on a public healthcare system, combined with a traditional emphasis on socialization in the Polanyian sense, hindered the swift integration of the private sector. This research investigates path dependency in Vietnam's public health sector, using theories including path dependency, Karl Polanyi's double movement with legal analysis method to analyze the interplay of historical decisions, and socialist policies in healthcare. Recognizing these institutional and market governance flaws, a deeper understanding of the role of law becomes vital in crafting strategies for a more resilient and sustainable healthcare system in Vietnam. In this article, Ho Chi Minh City is chosen as a case study due to its notable mix of public-private healthcare facilities and its status as a leading area in infection cases during the third COVID-19 wave. The article suggests that there should be a change in the way public and private sectors work together, one that is more in line with market-driven solutions which requires solid legal framework for cooperation beyond merely mobilizing resources.

γH2AX in mouse embryonic stem cells: Distribution during differentiation and following γ-irradiation.

Phosphorylated histone H2AX (γH2AX) represents a sensitive molecular marker of DNA double-strand breaks (DSBs) and is implicated in stem cell biology. We established a model of mouse embryonic stem cell (mESC) differentiation and examined the dynamics of γH2AX foci during the process. Our results revealed high numbers of γH2AX foci in undifferentiated mESCs, decreasing as the cells differentiated towards the endothelial cell lineage. Notably, we observed two distinct patterns of γH2AX foci: the typical discrete γH2AX foci, which colocalize with the transcriptionally permissive chromatin mark H3K4me3, and the less well-characterized clustered γH2AX regions, which were only observed in intermediate progenitor cells. Next, we explored responses of mESCs to γ-radiation (137Cs). Following exposure to γ-radiation, mESCs showed a reduction in cell viability and increased γH2AX foci, indicative of radiosensitivity. Despite irradiation, surviving mESCs retained their differentiation potential. To further exemplify our findings, we investigated neural stem progenitor cells (NSPCs). Similar to mESCs, NSPCs displayed clustered γH2AX foci associated with progenitor cells and discrete γH2AX foci indicative of embryonic stem cells or differentiated cells. In conclusion, our findings demonstrate that γH2AX serves as a versatile marker of DSBs and may have a role as a biomarker in stem cell differentiation. The distinct patterns of γH2AX foci in differentiating mESCs and NSPCs provide valuable insights into DNA repair dynamics during differentiation, shedding light on the intricate balance between genomic integrity and cellular plasticity in stem cells. Finally, the clustered γH2AX foci observed in intermediate progenitor cells is an intriguing feature, requiring further exploration.

Enhancement of a pyroelectric body energy harvesting scheme employing pulsed electric fields.

This research utilizes waste heat energy as a sustainable energy source to enhance pyroelectric power output by combining pyroelectric nanogenerators with an external pulsed electric field. When the surface temperature of the pyroelectric body varies, applying different pulses of the external electric field results in maximum power accumulation. A novel power-generating experimental setup was developed to measure and compute pyroelectric power generation. A standard Fuji ceramic C-9 sample was used to generate pyroelectric energy in a 20 °C temperature range from 120 to 140 °C. The continuous temperature variation frequency was 0.05 Hz, and the pulsed electric field was applied when the temperature rose. Pulses of the electric field with widths of 10, 50, 100, and 200 ms were applied to the sample under different pulse amplitudes, and the amplitude of each pulse was 250, 500, 1000, or 1500 V/mm. The maximum power generated through the application of an external pulsed electric field under the above-mentioned conditions was evaluated. This system had the highest power density of 0.204 mJ cm-2 °C-1 kV-1. In addition, for the lowest input power, the maximum power generation condition was a 10 ms pulse width and an amplitude of 250 V mm-1 in the applied electric field. This state might power smart sensor modules, IoT devices, automobiles, and other waste heat energy applications. Nano-pulse electric field applications may reduce input power to its lowest level, dependent on net-producing power. Therefore, new researchers can use net-generation power efficiency to create a large-scale power source using multiple pyroelectric arrays.

Acetyl-CoA is a key molecule for nephron progenitor cell pool maintenance.

Nephron endowment at birth impacts long-term renal and cardiovascular health, and it is contingent on the nephron progenitor cell (NPC) pool. Glycolysis modulation is essential for determining NPC fate, but the underlying mechanism is unclear. Combining RNA sequencing and quantitative proteomics we identify 267 genes commonly targeted by Wnt activation or glycolysis inhibition in NPCs. Several of the impacted pathways converge at Acetyl-CoA, a co-product of glucose metabolism. Notably, glycolysis inhibition downregulates key genes of the Mevalonate/cholesterol pathway and stimulates NPC differentiation. Sodium acetate supplementation rescues glycolysis inhibition effects and favors NPC maintenance without hindering nephrogenesis. Six2Cre-mediated removal of ATP-citrate lyase (Acly), an enzyme that converts citrate to acetyl-CoA, leads to NPC pool depletion, glomeruli count reduction, and increases Wnt4 expression at birth. Sodium acetate supplementation counters the effects of Acly deletion on cap-mesenchyme. Our findings show a pivotal role of acetyl-CoA metabolism in kidney development and uncover new avenues for manipulating nephrogenesis and preventing adult kidney disease.

The Role of Bystanders in the Prevention of Railway Suicides in New South Wales, Australia.

Background: Bystanders can play a key role in preventing railway suicides by taking direct action or by raising an alarm. Aims: The study investigated in this context: (1) the prevalence of preventative actions by bystanders; (2) the relationship, if any, between first-hand preventions by bystanders and the degree of ambiguity around the imminence of danger; and (3) the nature of first-hand preventions by bystanders. Method: Data were obtained from a security reporting database at Sydney Trains for 2011-2019 for accident and suicide-related incidents (N = 1,278). Results: In 635 cases of suicide prevention, bystanders were identified as first responders in 11% of cases and as raising the alarm in 11% of cases. Bystanders as first responders intervened proportionally more where the ambiguity of danger is low (jumping) compared with high (sitting, standing, wandering). Of the 69 cases of bystander preventions, 77% involved physical interaction (e.g., holding back) and 49% involved more than one bystander. Limitations: The data source could be biased because of incompleteness or nonstandard reporting. Conclusion: Rail policy-makers should consider education and support for bystanders and staff: for example, by making known the prevalence of helping, the importance of intervening, and what types of intervention are most helpful.

Histone deacetylases 1 and 2 target gene regulatory networks of nephron progenitors to control nephrogenesis.

Our studies demonstrated the critical role of Histone deacetylases (HDACs) in the regulation of nephrogenesis. To better understand the key pathways regulated by HDAC1/2 in early nephrogenesis, we performed chromatin immunoprecipitation sequencing (ChIP-Seq) of HDAC1/2 on isolated nephron progenitor cells (NPCs) from mouse E16.5 kidneys. Our analysis revealed that 11,802 (40.4%) of HDAC1 peaks overlap with HDAC2 peaks, further demonstrates the redundant role of HDAC1 and HDAC2 during nephrogenesis. Common HDAC1/2 peaks are densely concentrated close to the transcriptional start site (TSS). GREAT Gene Ontology analysis of overlapping HDAC1/2 peaks reveals that HDAC1/2 are associated with metanephric nephron morphogenesis, chromatin assembly or disassembly, as well as other DNA checkpoints. Pathway analysis shows that negative regulation of Wnt signaling pathway is one of HDAC1/2's most significant function in NPCs. Known motif analysis indicated that Hdac1 is enriched in motifs for Six2, Hox family, and Tcf family members, which are essential for self-renewal and differentiation of nephron progenitors. Interestingly, we found the enrichment of HDAC1/2 at the enhancer and promoter regions of actively transcribed genes, especially those concerned with NPC self-renewal. HDAC1/2 simultaneously activate or repress the expression of different genes to maintain the cellular state of nephron progenitors. We used the Integrative Genomics Viewer to visualize these target genes associated with each function and found that HDAC1/2 co-bound to the enhancers or/and promoters of genes associated with nephron morphogenesis, differentiation, and cell cycle control. Taken together, our ChIP-Seq analysis demonstrates that HDAC1/2 directly regulate the molecular cascades essential for nephrogenesis.

Bisect offset ratio and cartilaginous sulcus angle are good combined predictors of recurrent patellar dislocation in children and adolescents.

OBJECTIVES: Recurrent patellar dislocation (RPD) is found most commonly in the juvenile population. While risk factors have been well-established in adults, there remains a paucity in radiographical data to define normal and pathoanatomical juvenile cohorts. The objectives of this paper were to elucidate the differences in the patellofemoral joint between RPD and typically developed (TD) juvenile populations, using MRI measurements, and determine the best independent and combined predictors of RPD. METHODS: A prospective, cross-sectional study was conducted with 25 RPD and 24 TD participants aged between 8 and 19 years. MR images were obtained to assess common measures of lower limb alignment, patellofemoral alignment, and trochlear dysplasia. RESULTS: Significant differences were evident for acetabular inclination, tibial-femoral torsion, tibial tubercle-to-trochlear groove (TT-TG) distance, lateral patellar tilt (LPT), cartilaginous sulcus angle (CSA) and bisect offset ratio (BOR). CSA and BOR were included in the final predictive model, which correctly classified 89.4% of RPD cases. CONCLUSION: Radiographical parameters that stratify risk of RPD in adults are also able to predict RPD in the pediatric population (TT-TG, LPT, CSA and BOR). Together, CSA and BOR accurately identified 89.4% of RPD. These measures should be included in the evaluation of pediatric patients who present with patellar dislocation. LEVEL OF EVIDENCE: Level II.

Patterns of pre-crash behaviour in railway suicides and the effect of corridor fencing: a natural experiment in New South Wales.

Suicides on railway systems remain a significant concern world-wide. Understanding patterns of pre-crash behaviour, whether jumping, lying or wandering on tracks, is important for the design of preventative measures, yet prior studies have reported divergent patterns of behaviour. This study tested the hypothesis that higher standards of corridor fencing reduce the proportion of train suicides in the non-jumping category. Data was analyzed as a natural experiment for 171 cases of apparent railway suicides in New South Wales (NSW) for the period 2011-2018. Results were congruent with the hypothesis. A higher level of corridor fencing in metropolitan Sydney was associated with a lower proportion in the non-jumping category (33%) compared with regional areas (74%). The article contributes by showing that: (i) fencing appears to lead to a reduction in some types of rail suicides and thus; (ii) contributes to a lower overall rate of suicide by train; and (iii) even with fencing, the non-jumping incidents warrant attention for appropriate countermeasures.

The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders.

Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35-46%) of patients), as well as the deficit in melatonin (51% (45-57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41-54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS-melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS-melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD.